The human leukocyte common antigen (LCA) consists of a family of at least five transmembrane glycoproteins whose differences in primary structure depend on alternative splicing of mRNA transcripts from a single gene. LCA expression by all leukocyte subsets and the existence of homologous LCA molecules among several animal species suggest an important, evolutionarily-conserved role in leukocyte biology which may be relevant to the entire spectrum of diseases involving leukocytes. More specifically, evidence exists that LCA proteins represent a set of cell surface receptors with protein tyrosine phosphatase activity that are involved in signal transduction and play a role in lymphoid proliferation, differentiation and cytotoxicity. This suggests that their study may enhance our understanding of cell proliferation and differentiation regulatory networks, and may prove to be clinically relevant to the management of infections, allergic and autoimmune disorders, allograft rejection, tumor-host interactions and tumor prevention. The detailed structural characterization of LCAs obtained from lymphoid subsets has been performed; however, there is little information available concerning LCA expression by immune-associated dendritic cells isolated from lymphoid tissue cell suspensions and peripheral blood. Recently, we have performed epitope mapping studies which strongly suggest that human Langerhans cells express a novel form of LCA. This raises the possibility that related mammalian dendritic cells may also express novel LCA isoforms. We propose to use two-color immunophenotyping, immunoprecipitation/SDS-PAGE, Northern blotting, PCR amplification, cDNA sequencing and S1 nuclease protection analysis to study the structure of LCA isoforms expressed by immune-associated dendritic cells in the human, mouse and rat. These studies will provide information concerning the relatedness of various immune-associated dendritic cells to one another and to other antigen-presenting cells such as monocytes/macrophages. This research will be the foundation for future efforts to raise anti-LCA monoclonal antibodies specific for dendritic cells, and to study the functional effects of cell transfection with different LCA cDNAs. This, in turn, will allow novel studies of immune- associated dendritic cell ontogeny/phylogeny and further our understanding of the functional significance of LCA isoform diversity.